• Egg production
• Gut health
• Hen welfare
• Inflammatory markers
• Plant bioactive compounds

• Animals
• Chickens/physiology
• Chickens/immunology
• Female
• Diet/veterinary
• Anti-Inflammatory Agents/pharmacology
• Anti-Inflammatory Agents/administration & dosage
• Animal Feed/analysis
• Random Allocation
• Dietary Supplements/analysis
• Immunomodulating Agents/pharmacology
• Immunomodulating Agents/administration & dosage
• Plant Extracts/pharmacology
• Plant Extracts/administration & dosage

• Eucalyptus
• Feed Additive
• Hot Condition
• Moringa
• Propolis
• Yucca

• Dendritic cells
• Immunomodulation
• MAGE-1
• Propolis
• Retinoic acid
• T CD4+ cells

• allergy
• anti-allergic
• anti-inflammatory
• antioxidative effects of propolis
• inflammatory cells
• propolis
• propolis sensitization

• cancer
• cancer therapy
• chemoprevention
• epigenetic and genetic mechanisms
• molecular targets
• polyphenolic/flavonoid compounds
• propolis

• antioxidants
• bee pollen
• broilers
• immune response
• productive performance
• propolis

Cancer is one of the leading causes of death globally. Anticancer drugs aim to block tumor growth by killing cancerous cells in order to prevent tumor progression and metastasis. Efficient anticancer drugs should also minimize general toxicity towards organs and healthy cells. Tumor growth can also be successfully restrained by targeting and modulating immune response. Cancer immunotherapy is assuming a growing relevance in the fight against cancer and has recently aroused much interest for its wider safety and the capability to complement conventional chemotherapeutic approaches. Natural products are a traditional source of molecules with relevant potential in the pharmacological field. The huge structural diversity of metabolites with low molecular weight (small molecules) from terrestrial and marine organisms has provided lead compounds for the discovery of many modern anticancer drugs. Many natural products combine chemo-protective and immunomodulant activity, thus offering the potential to be used alone or in association with conventional cancer therapy. In this review, we report the natural products known to possess antitumor properties by interaction with immune system, as well as discuss the possible immunomodulatory mechanisms of these molecules.

• anticancer
• antitumor
• immunomodulators
• marine products
• natural products

• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Aquatic Organisms/chemistry
• Biological Products/chemistry
• Biological Products/pharmacology
• Biological Products/therapeutic use
• Humans
• Immunity
• Neoplasms/drug therapy

• Adjunctive therapy
• Natural product
• Nutraceutical
• Pharmaceutical
• Primary therapy
• Propolis
• Respiratory tract
• Systematic review

• Animals
• Anti-Infective Agents/administration & dosage
• Anti-Infective Agents/pharmacology
• Bees
• Humans
• Propolis/administration & dosage
• Propolis/pharmacology
• Respiratory Tract Diseases/drug therapy

• 4-ABP
• CYP2E1
• Ku70/Ku80
• OGG1
• propolis

• Aminobiphenyl Compounds/pharmacology
• Carcinogens
• Cytochrome P-450 CYP2E1/metabolism
• DNA Damage
• Humans
• Liver
• Oxidative Stress
• Propolis/pharmacology

• SARS-CoV-2
• antiviral
• chemical constituents
• clinical applications
• immunomodulatory
• molecular docking
• propolis

• VR grant 2016-05885 This work was supported by the Swedish Research Council Vetenskapsrådet

• artepillin C (ARC)
• biomedical properties
• caffeic acid phenethyl ester (CAPE)
• honeybee
• natural drug
• propolis
• traditional healthcare

• Animals
• Anti-Anxiety Agents/pharmacology
• Antineoplastic Agents/pharmacology
• Antioxidants/pharmacology
• Brazil
• Caffeic Acids/pharmacology
• Humans
• New Zealand
• Phenylethyl Alcohol/analogs & derivatives
• Phenylethyl Alcohol/pharmacology
• Phenylpropionates/pharmacology
• Propolis/pharmacology

• Brazilian brown propolis
• antimalarial activity
• cytotoxicity
• diterpenes
• lignans

• animal welfare
• egg production
• laying hen
• reproduction
• royal jelly

• bioactive properties
• chemical composition
• poplar-type propolis
• vegetal material

• Baccharis dracunculifolia
• Dalbergia ecastophyllum
• bioactive properties
• chemical composition
• propolis

• acetic acid
• antinociceptive pain
• formalin test
• propolis
• rats

• Adjuvant
• Alcoholic extracts
• Aqueous extract
• Multi-epitope HIV-1 vaccine
• Propolis

Propolis is one of the bee products that widely used in health therapy. However, there has no study evaluating the developmental toxicity of propolis. This study was aimed to analyze the effect of propolis administration during pregnancy on fetal development. The pregnant mice were divided into five groups including control group (Tween 80 1%), low-dose (380 mg/kg b.wt.) and high-dose (1400 mg/kg b.wt.) of water extract of propolis from Banten (WEB), and low-dose (380 mg/kg b.wt.) and high-dose (1400 mg/kg b.wt.) of ethanol extract of propolis from South Sulawesi (EES). Propolis was administered for 18 days of gestation and then sacrificed to analyze the fetal development by examining external and skeletal abnormalities. The histopathological examination of placenta was also conducted. The result showed both low-dose groups did not inhibit fetal development. However, the high-dose of EES significantly reduced the weight, crown-rump of fetuses and increased the number of resorption (p < 0.05). Fetal weight was the only significantly reduced parameter of fetal growth in the highdose group of WEB (p < 0.05). The histopathological examination of placenta showed a reduction of labyrinth development in both high-dose groups. Dose of 380 mg/kg dose of Indonesian propolis is relatively safe for consumption during pregnancy.

• Developmental biology
• Food science
• Natural product chemistry
• Nutrition
• Pharmaceutical science
• Stingless bee propolis
• Teratogenicity
• Toxicology

• Artemisia ordosica extract
• antioxidant
• apparent nutrient digestibility
• immunity
• weanling piglet

The aim of this study was to assess the antioxidant, photoprotective, and antiaging effects of Greek propolis. Propolis was subjected to n-heptane or methanol extraction. Total phenolic/flavonoid content and antioxidant potential were determined in the extracts. Promising extracts were evaluated for their cytoprotective properties using human immortalized keratinocyte (HaCaT) or reconstituted human skin tissue following exposure to UVB. Assessment of cytotoxicity, DNA damage, oxidative status, and gene/protein expression levels of various matrix metalloproteinases (MMPs) were performed. The propolis methanolic fractions exhibited higher total phenolic and flavonoid contents and significant in vitro antioxidant activity. Incubation of HaCaT cells with certain methanolic extracts significantly decreased the formation of DNA strand breaks following exposure to UVB and attenuated UVB-induced decrease in cell viability. The extracts had no remarkable effect on the total antioxidant status, but significantly lowered total protein carbonyl content used as a marker for protein oxidation in HaCaT cells. MMP-1, -3, -7, and -9, monitored as endpoints of antiaging efficacy, were significantly reduced by propolis following UVB exposure in a model of reconstituted skin tissue. In conclusion, propolis protects against the oxidative and photodamaging effects of UVB and could be further explored as a promising agent for developing natural antiaging strategies.

• DNA damage
• HaCaT
• antiaging
• antioxidant
• matrix metalloproteinases
• photoprotective
• propolis
• reconstituted skin

To evaluate the effect of red propolis and L-lysine on angiogenesis and tumor growth in a new model of hamster cheek pouch inoculated with Walker 256 tumor cells.

The study consisted of two experiments with four groups each (total: 57 hamsters). In the experiment 1, the animals were inoculated with Walker tumor cells, followed by administration of test substances (red propolis 200mg/5mL/kg or L-lysine 150mg/kg) or control substances (gum arabic 5mL/kg or water 5mL/kg) for 10 days. The animals in the experiment 2 received red propolis, L-lysine, gum arabic or water at the same doses, for 33 days prior to inoculation of Walker tumor cells, followed by 10 days of treatment with the same substances. Based on single-plane images, angiogenesis was quantified (mean vascular area), in percentage, and tumor area (mm²) and perimeter (mm).

In the experiment 1, compared to animals receiving water, the mean vascular area expressed in percentage was significantly smaller in animal treated with propolis (p<0.05) and L-lysine (p<0.001).

Both red propolis and L-lysine inhibited tumor angiogenesis in the new hamster cheek pouch model when administered after tumor inoculation.

With a concomitant increase in immune-related diseases such as allergic diseases, Type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease and other immune-related responses such as immunodeficiency, various infectious, diseases, vaccines, and malignancies, it has become very important to have a well-balanced and properly functioning immune system for the maintenance of human health. Recent scientific research has strongly suggested propolis as one of the most promising immunomodulation agents. This review describes recent findings with respect to propolis and its ingredients that show potential in this respect and evaluate their potential mechanisms. The author believes that propolis or/and its ingredients alone and in combination could be promising in manipulating the immune response and inducing immunomodulation. Further exploratory studies are needed to support large clinical trials toward further development of propolis.

• Allergic diseases
• immunodeficiency
• immunomodulation
• malignancies
• propolis

• Angiogenesis
• Green
• Hydroalcoholic extract
• Inflammation
• Low-protein diet
• Propolis
• Sponge implantation

• Animals
• Body Weight/drug effects
• Body Weight/physiology
• Diet, Protein-Restricted/adverse effects
• Ethanol/administration & dosage
• Female
• Inflammation/chemically induced
• Inflammation/drug therapy
• Inflammation/metabolism
• Inflammation Mediators/antagonists & inhibitors
• Inflammation Mediators/metabolism
• Mice
• Propolis/administration & dosage
• Protein Deficiency/chemically induced
• Protein Deficiency/drug therapy
• Protein Deficiency/metabolism
• Random Allocation
• Water/administration & dosage

• Artepillin C (PubChem CID: 5472440)
• Cytotoxic activity
• Drupanin (PubChem CID: 6440361)
• IFN-γ
• NK cells
• Propolis
• p-coumaric acid (PubChem CID: 637542)

• Animals
• Cytotoxicity, Immunologic/drug effects
• DNA-Binding Proteins/genetics
• Interferon-gamma/genetics
• Killer Cells, Natural/drug effects
• Killer Cells, Natural/immunology
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Propolis
• Receptors, Interferon/genetics
• Solubility
• Solvents/chemistry
• Water/chemistry

• neutrophils
• propolis
• vulvovaginal candidiasis

TiO₂ nanotubes (TNT) formation is beneficial for improving bone cell–material interaction and drug delivery for Ti dental implants. Among the natural drugs to be installed in TNT, selected propolis has antibacterial and anti-inflammatory properties. It is a resinous natural product which is collected by the honeybees from the various types of plants with their salivary enzymes. This study concludes that TNT loaded with a propolis (PL-TNT-Ti) dental implant has the ability to improve osseointegration. The propolis particles were embedded within the TNT or adhered to the top. In a cytotoxicity test using osteoblast, PL-TNT-Ti group exhibited an increased cell proliferation and differentiation. A Sprague Dawley rat mandibular model was used to evaluate the osseointegration and bone bonding of TNT or PL-TNT-Ti. From the µ-CT and hematoxylin and eosin (HE) histological results after implantation at 1 and 4 weeks to rat mandibular, an increase in the extent of new bone formation and mineral density around the PL-TNT-Ti implant was confirmed. The Masson’s trichrome staining showed the expression of well-formed collagenous for bone formation on the PL-TNT-Ti. Immunohistochemistry staining indicate that bone morphogenetic proteins (BMP-2 and BMP-7) around the PL-TNT-Ti increased the expression of collagen fibers and of osteogenic differentiation whereas the expression of inflammatory cytokine such as interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) is decreased.

• dental implant
• mandibular injuries
• nanotubes
• osseointegration
• propolis

Propolis is a resinous material collected by honeybees from several plant sources. This research aimed at showing its protective effect against UVA-induced apoptosis of human keratinocyte HaCaT cells. Using Hoechst staining, it was demonstrated that propolis (5 and 10 μg/mL) significantly inhibited the apoptosis of HaCaT cells induced by UVA-irradiation. Propolis also showed the protective effect against loss of mitochondrial membrane potential induced by UVA-irradiaiton in HaCaT cells. Propolis also inhibited the expression of activated caspase-3 induced by UVA-irradiation. To investigate the role of ROS in UVA-induced apoptosis and protection by propolis, the generation of ROS was determined in cells. The results showed that the generation of ROS was markedly reduced in cells pretreated with propolis. Consequently, propolis protected human keratinocyte HaCaT cells against UVA-induced apoptosis, which might be related to the reduction of ROS generation by UVA-irradiation.

• Apoptosis
• Keratinocyte
• Propolis
• ROS
• UVA

• Acute lymphoblastic leukemia
• Apoptosis
• Propolis
• miRNA

Propolis and Hypericum perforatum L. are natural products which contain many active compounds and have numerous beneficial effects, including an antitumor effect. Gliobmastoma multiforme (GBM) is a common primary brain tumor with poor prognosis and limited treatment options. In this study, the effect of propolis (EEP) combined with H. perforatum L. (HPE) on glioblastoma cell line U87MG was investigated for the first time.

Anti-proliferative activity of EEP, HPE and their combination (EEP + HPE) was determined by a cytotoxicity test, DNA binding by [³H]-thymidine incorporation and cell migration assay. Anti-metastatic properties in U87MG treated with EEP, HPE and EEP + HPE were estimated on cells migration test (scratch assay) and metalloproteinases (MMP2 and MMP9) secretion (gelatin zymography).

Combination of HPE and EEP extracts was found to have a time- and dose-dependent inhibitory effect on the viability of U87MG cells. This effect was significantly higher (p < 0.05) when compared to these two extracts applied separately, which was confirmed by the significant reduction of DNA synthesis and significantly higher mitochondrial membrane permeabilization. A significant decreasing in migration cells and in pro-MMP9 and pro-MMP2 secretion in U87MG cells were demonstrated after exposure to combination of EEP (30 μg/ml) with HPE (6.25 μg/ml).

In this study, the combination of ethanolic extract from propolis and ethanolic extract of fresh-cut H. perforatum L. was proved the ability to reduce invasiveness of glioma cells through the inhibition of MMP2 and MMP9 secretion and suppression of cell migration. It has a more potent anti-proliferative effect on U87MG glioma cell line compared to using propolis and H. perforatum L. separately. Further studies are required to verify whether the examined extracts can activate apoptotic pathways.

The online version of this article (doi:10.1186/s12906-016-1351-2) contains supplementary material, which is available to authorized users.

• Glioblastoma multiforme
• H. perforatum L.
• Propolis

• Apoptosis
• HUVECs
• Homocysteine
• LPO
• Propolis
• ROS

• Antioxidants/pharmacology
• Apoptosis/drug effects
• Apoptosis Regulatory Proteins/genetics
• Apoptosis Regulatory Proteins/metabolism
• Cell Proliferation
• Cells, Cultured
• Drug Evaluation, Preclinical
• Gene Expression/drug effects
• Human Umbilical Vein Endothelial Cells/drug effects
• Human Umbilical Vein Endothelial Cells/physiology
• Humans
• Lipid Peroxidation
• Oxidative Stress
• Propolis/pharmacology
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Reactive Oxygen Species/metabolism
• Turkey

Breast cancer is a heterogeneous disease and the leading cause of cancer mortality worldwide. Triple negative breast cancer (TNBC) is considered to be one of the most aggressive breast neoplasia due to failure of chemotherapy response. Thus, there is an urgent need of finding alternative therapies for TNBC. This study was designed to evaluate the synergistic effect induced by propolis and bee venom on luminal (MCF-7) and TNBC (Hs578T) cell lines.

In order to evaluate the synergistic effect of aqueous extract of propolis and bee venom, we treated in combination two breast cancer cell lines: MCF-7(luminal subtype) and Hs578T (TNBC subtype).

Our results indicate that both cell lines exhibited similar sensitivity to the aqueous extract of propolis at a dilution of 0.072–0.09 mg/ml. The results concerning IC50 for bee venom on MCF-7 cells was 1 mg/ml, 20 times higher than 0.05 mg/ml in Hs578T cells. By combining the aqueous extract of propolis with bee venom, we obtained synergistic effects at a higher concentration, which was 5 and 2 times stronger than the two treatments alone.

Overall, the results from our study indicated that the combination of aqueous extract of propolis and bee venom treatments induced synergistic antiproliferative effects in a concentration-dependent manner in breast cancer cells. Thus we can hypothesize that the combination of honeybee propolis and venom might be involved in signaling pathways that could overcome cells resistance to therapy.

• apoptosis
• breast cancer
• propolis
• venom

Water soluble form of poplar propolis prepared with the aid of “pluronic” p85 copolymer.

The aim of this study was to examine hepatoprotective effect of ethanolic extract of propolis (KPEt) from Kashmir Himalaya against isoniazid and rifampicin (INH-RIF) induced liver damage in rats. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg) intraperitoneal (i.p.) injection for 14 days. We report the protective effects of KPEt against INH-RIF induced liver oxidative stress, inflammation, and enzymatic and nonenzymatic antioxidants. Oral administration of KPEt at both doses (200 and 400 mg/kg body weight) distinctly restricted all modulating oxidative liver injury markers and resulted in the attenuation of INH-RIF arbitrated damage. The free radical scavenging activity of KPEt was evaluated by DPPH, nitric oxide, and superoxide radical scavenging assay. The components present in KPEt identified by ultra high performance liquid chromatography diode array detector time of flight-mass spectroscopy (UHPLC-DAD-QToF-MS) were found to be flavonoids and phenolic acids. The protective efficacy of KPEt is possibly because of free radical scavenging and antioxidant property resulting from the presence of flavonoids and phenolic acids.

Propolis is a resin produced by honeybees by mixing wax, pollen, salivary secretions, and collected natural resins.

The precise composition of propolis varies with the source, and over 300 chemical components belonging to the flavonoids, terpenes, and phenolic acids have been identified in propolis. Moreover, its chemical composition is subjected to the geographical location, botanical origin, and bee species.

Propolis and its compounds have been the focus of many works due to their antimicrobial and anti-inflammatory activity; however, it is now recognized that propolis also possesses regenerative properties.

There is an increasing interest in the healing potential of natural products, considering the availability and low cost of these products. Propolis contains a huge number of compounds that explicate some biological effects that speeds up the healing process and is widely used in folk remedies.

This review aims to condense the results on the mechanism of activity of propolis and its compounds.

• Propolis
• Tissue regeneration
• Wound healing

In general, chemical plaque agents have been used in mouthwashes, gels, and dentifrices. In some situations, application of mouthwashes and dentifrices can be difficult. Therefore, different approaches for oral health-care have been needed. The aim of this study was to evaluate the effect of propolis chewing-gum compared to propolis-containing mouthwash on gingival inflammation and plaque accumulation on patients that refrained from daily oral hygiene procedures for 5 days.

10 college students with systemically healthy and very good oral hygiene and gingival health were included in this randomized, single-blind, crossover 5-day plaque regrowth with a 3-day washout period clinical study. After plaque scores were reduced to zero, participants were asked to refrain from oral hygiene procedures and allocated to either propolis mouthwash or chewing-gum group. Chewing-gum was performed after meals 3 times a day for 20 min mouthwash group was instructed to rinse mouthwash 2 times a day for 1 min. On day 5, the clinical periodontal measurements containing plaque and gingival indexes were taken from the participants.

The both plaque and gingival indexes of propolis mouthwash group were significantly lower than that of the propolis chewing-gum group (P = 0.005).

It was demonstrated that the propolis mouthwash was more effective than the propolis chewing gum on the plaque inhibition and the gingival inflammation.

• Chewing gum
• dental plaque
• gingival inflammation
• mouthwashes
• propolis

Propolis is the bee product noted for multiple biological effects, and therefore it is widely used for the prevention and treatment of a variety of diseases. The active substances of propolis are easily soluble in ethanol. However ethanolic extracts cannot be used in treatment of certain diseases encountered in ophthalmology, pediatrics, etc. Unfortunately, the main biologically active substances of propolis are scarcely soluble in water, oil and other solvents usually used in pharmaceutical industry. The aim of this study was to investigate chemical composition, radical scavenging and antimicrobial activity of propolis extracts differently made in nonethanolic solvents.

Total content of phenolic compounds in extracts was determined using Folin-Ciocalteu method. Chemical composition and radical scavenging activity of extracts were determined using HPLC system with free radical reaction detector. Antimicrobial activity of examined preparations was evaluated using the agar-well diffusion assay.

Total amount of phenolic compounds in extracts made in polyethylene glycol 400 (PEG) and water mixture or in PEG, olive oil and water mixture at 70 °C was comparable to that of ethanolic extract. Predominantly identified compounds were phenolic acids, which contribute ca. 40 % of total radical scavenging activity.

Investigated nonethanolic extracts inhibited the growth and reproduction of all tested microrganisms. Antimicrobial activity of some extracts was equal or exceeded the antimicrobial effect of ethanolic extract. Extracts made in pure water or oil only at room temperature, contained more than 5 – 10-fold lower amount of phenolic compounds, and demonstrated no antimicrobial activity.

Nonethanolic solvent complex and the effect of higher temperature allows more effective extraction of active compounds from propolis. Concentration of total phenolic compounds in these extracts does not differ significantly from the concentration found in ethanolic extract. Propolis nonethanolic extracts have radical scavenging and antimicrobial activity.

The online version of this article (doi:10.1186/s12906-015-0677-5) contains supplementary material, which is available to authorized users.

• Anticholinesterase
• Antioxidant
• Cytotoxicity
• Densitometry
• Propolis
• Quercetin

Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC₅₀ values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment.